ABSTRACT
Background: Previous studies have shown an inferior response to mRNA SARS-CoV-2 vaccination in solid organ transplant (SOT) recipients up to four months after vaccination. We examined the development in anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in SOT recipients six months after vaccination compared to immunocompetent controls. Methods: in 200 SOT recipients and 200 age-and sex-matched controls, we measured immunogenicity of two doses of BNT162b2 vaccine up to 6 months after vaccination. An in-house enzyme-linked immunosorbent assay (ELISA) based system was used to measure concentrations of anti-receptor binding domain (RBD) IgG. Neutralizing capacity of antibodies was estimated using an in-house ELISA based pseudo-neutralization assay. Presence of anti-SARS-CoV-2 nucleocapsid (N) antibodies was assessed using an electrochemiluminescence based kit from Roche diagnostics. Presence of N-antibodies was used as evidence of previous natural infection. In a subset of participants an interferon-gamma releasing assay was used to assess T-cell responses. Results: SOT recipients and controls demonstrated an increase in anti-RBD IgG after both first and second dose of BNT162b2. Six months after the first dose, GMC of anti-RBD IgG declined in both groups but remained higher in controls (55.85 AU/mL, 95% CI 36.95-83.33 vs. 1448.94 AU/mL, 95% CI 1139.43-1799.48). Furthermore, more controls had a cellular response six months after vaccination (13.1% of SOT recipients vs. 59.4% of controls, p<0.001). We found increasing age (RR 1.23 pr year, 95% CI 1.11-1.35, p<0.001), being within one year of transplantation (RR 1.55, 95% CI 1.30-1.85, p<0.001), use of mycophenolate (RR 1.53, 95% CI 1.18-1.99 p=0.001), kidney transplanation (RR 1.70, 95% CI 1.25-2.30, p=0.001), lung-transplantation (RR 1.63, 95% CI 1.16-2.29, p=0.005) and cancer comorbidity (RR 1.52, 95% CI 1.26-1.82, p <0.001) to be significantly associated with humoral non-response. Conclusion: Humoral and cellular responses to two doses of BNT162b2 are inferior in SOT recipients compared to controls. Furthermore, anti-RBD concentration decline 6 months after first vaccine dose. Further investigations of clinical significance of anti-RBD IgG concentration and vaccine non-response is warranted to optimize the timing and use of booster vaccines. Multiple risk factors for non-response were identified and may help identify SOT recipients at high risk of vaccine non-response.